Preparation of corticoids from 17-keto steroids

ABSTRACT

Disclosed is a 20,21-dihalo steroid (VII) and a steroidal sulfoxide (VIII) as well as processes to produce them. The 20,21-dihalo steroid (VII) and sulfoxide (VIII) are intermediates useful in the preparation of pharmaceutically useful corticoids.

This is a division of application Ser. No. 264,593 filed May 18, 1981 now U.S. Pat. No. 4,357,279.

The present invention relates to intermediates and processes for preparation of those intermediates useful in the preparation of pharmaceutically useful corticoids for which the essential material constituting a disclosure thereof is incorporated here by reference from divisional U.S. patent application Ser. No. 264,593, filed May 18, 1981, now U.S. Pat. No. 4,357,279. 

We claim:
 1. A 20,21-dihalo steroid of the formula ##STR1## where A is a fluorine, chlorine or bromine atom; M is a fluorine, chlorine or bromine atom; R₆ is a hydrogen or fluorine atom or methyl group; R₉ is a hydrogen or fluorine atom, hydroxyl group, --OSi(R)₃ or nothing; R₁₁ is (H), (H,H), (H, β--OSi(R)₃, or (O); R₁₆ is a hydrogen atom or methyl group; R₂₂ is alkyl of 1 thru 5 carbon atoms, trichloromethyl, phenyl, phenyl substituted with 1-4 carbon atoms or substituted with 1 thru 3 nitro or trifluoromethyl groups, aralkyl of 7 thru 12 carbon atoms or --N---(R₁₂₂)₂ or phthalimide; ˜ indicates the attached group can be in either the α or β configuration; is a single or double bond.
 2. A 20,21-dihalo steroid according to claim 1 wherein A is a chlorine atom.
 3. A 20,21-dihalo steroid according to claim 2 where A and M are both a chlorine atom.
 4. A 20,21-dihalo steroid according to claim 1 where R₂₂ is phenyl.
 5. A 20,21-dihalo steroid of formula (VII) according to claim 1 where R₆ and R₁₆ are hydrogen atoms, where R₉ is nothing and R₁₁ is [H] which gives a Δ⁹,11 functionality in the C ring.
 6. A 20,21-dihalo steroid according to claim 5 which is 20,21-dichloro-21-(phenylsulfinyl)pregna-4,9(11),17(20)-trien-3-one.
 7. A sulfoxide of the formula ##STR2## where Z is --OR₂₀ or SR₂₀ ; and where A, R₆, R₉, R₁₁, R₁₆, R₂₂, ˜ and are defined in claim
 1. 8. A sulfoxide according to claim 7 where A is a chlorine atom.
 9. A sulfoxide according to claim 7 where Z is methoxy or phenoxy.
 10. A sulfoxide according to claim 7 where R₂₂ is phenyl.
 11. A sulfoxide of formula (VIII) according to claim 7 where R₆ and R₁₆ are hydrogen atoms, where R₉ is nothing and R₁₁ is [H] which gives a Δ⁹,11 functionality in the C ring.
 12. A sulfoxide according to claim 7 which is 21-chloro-20-methoxy-21-(phenylsulfinyl)pregna-4,9(11),17(20)-trien-3-one.
 13. A process for the preparation of a 20,21-dihalo steroid of the formula ##STR3## which comprises (1) contacting a C21-steroid of the formula ##STR4## with a sulfenylating agent of the formula R₂₂ --S--X (VI), where A, M, R₆, R₉, R₁₁, R₁₆, R₂₂, ˜ and are defined in claim 1 and where X is a chlorine or bromine atom, phenylsulfone, phthalimide or imidazole group.
 14. A process according to claim 13, where for the 20,21-dihalo steroid (VII), R₆ and R₁₆ are hydrogen atoms, were R₉ is nothing and R₁₁ is [H] which gives a Δ⁹,11 functionality in the C ring.
 15. A process according to claim 13 where for the sulfenylating agent, R₂₂ --S--X, X is a chlorine or bromine atom, and R₂₂ is a phenyl group.
 16. A process according to claim 13 where the temperature range for the sulfenylation reaction is from about -80° to about 25°.
 17. A process for the preparation of a sulfoxide of the formula ##STR5## which comprises contacting a 20,21-dihalo steroid of the formula ##STR6## with an alkoxide or mercaptide of the formula OR₂₀.sup.⊖ or SR₂₀.sup.⊖, respectively, where A, M, R₆, R₉, R₁₁, R₁₆, R₂₂, ˜ and are defined in claim 1; and where Z is defined in claim 7, and where R₂₀ is alkyl of 1 thru 4 carbon atoms or phenyl.
 18. A process according to claim 17, where for the 21-halo steroid (VIII), R₆ and R₁₆ are hydrogen atoms, where R₉ is nothing and R₁₁ is [H] which gives a Δ⁹,¹¹ functionality in the C ring.
 19. A process according to claim 17, where the base is an alkoxide.
 20. A process according to claim 19, where the alkoxide is methoxide or phenoxide.
 21. A process according to claim 17, where the reaction with base is performed in a polar solvent.
 22. A process according to claim 17, where 1.0 equivalents of base are used. 